Washington Editor

Shares of Vasogen Inc. plunged Monday after the FDA raised concerns about the design of the firm's confirmatory Phase III clinical trial of Celacade, an investigational device to treat heart failure.

Vasogen (NASDAQ:VSGN) closed at $1.33 Monday, down 45 cents, or 25.3 percent.

CEO Chris Waddick said the FDA during a meeting last spring with Vasogen had recommended the Mississauga, Ontario-based firm use a Bayesian design, a statistical theory and approach to data analysis that provides a coherent method for learning from evidence as it accumulates.

The Bayesian approach allows use of prior trial results with a confirmatory study to obtain additional information about efficacy and safety and has the potential to reduce the number of patients required in addition to a confirmatory trial's costs and duration.

But Friday, Waddick told BioWorld Today, regulators informed the company that it now disagreed with a Bayesian approach because of concerns that Vasogen "would not be able to recruit a similar patient population" as it had done in its earlier Phase III study of its Celacade technology.

The FDA, he said, maintained that the standard of care for patients with New York Heart Association (NYHA) Class II heart failure - patients with slight, mild limitation of activity - has "evolved" since Vasogen reported results in June 2006 from its earlier Celacade Phase III trial.

The results from that Phase III trial, known as the Advanced Chronic Heart Failure Clinical Assessment of Immune Modulation Therapy study, or ACCLAIM, showed that Celacade failed to achieve its primary endpoint of significantly reducing the risk of death and cardiovascular hospitalization in the total treatment population. (See BioWorld Today, June 27, 2006.)

However, Celacade reduced the risk of death or cardiovascular hospitalization by 39 percent, which was statistically significant, in the subgroup of patients with NYHA Class II heart failure.

The ACCLAIM study included 2,408 patients with NYHA classes II, III or IV heart failure with a left-ventricular ejection fraction (LVEF) of 30 percent or less, and who had been hospitalized or received intravenous drug therapy for heart failure within the previous 12 months, or had NYHA Class III/IV heart failure with a LVEF of less than 25 percent.

Patients enrolled in ACCLAIM also were receiving optimal standard-of-care therapy for heart failure, which included diuretics, angiotensin-converting enzyme-inhibitors or angiotensin-receptor blockers, beta blockers, automatic implantable cardioverter defibrillators and cardiac resynchronization therapy.

Based on the discussion the firm had with the FDA last spring, Waddick said, his company had planned to move forward with the confirmatory Phase III ACCLAIM II study with 300 to 600 patients with NYHA Class II heart failure to support its U.S. application for Celacade, a device that targets the inflammation underlying chronic heart failure and other cardiovascular diseases.

The product is approved for use in Europe.

Waddick said the FDA has not yet scheduled a meeting with Vasogen to discuss the agency's recent comments on the ACCLAIM II study design and a plan for moving forward with the trial. However, he said, his firm disagrees with regulators about their initial comments that the standard of care has changed for patients with NYHA Class II heart failure and that a Bayesian approach will no longer be appropriate for the confirmatory study.

"We don't share their concerns," he declared, adding that Vasogen is looking forward to having a discussion with the FDA about its comments and presenting information to support moving forward with a Bayesian design.

Waddick emphasized that the FDA's comments to the firm is "not a rejection" of the company's study or product in any way.

He called the market's response Monday to Vasogen's announcement about the FDA's comments an "overreaction" to information that is "early in the process," which may have been misinterpreted by some.

Although Celacade will be regulated as a medical device, the FDA's Center for Biologics Evaluation and Research (CBER) will be the lead reviewer for the product, with the agency's Center for Devices and Radiological Health providing input, Waddick noted.

The FDA in December notified Vasogen that because of new guidelines issued in August as part of the agency's "Guidance for Industry Regulation of Human Cells, Tissues, and Cellular and Tissue-Based Products - Small Entity Compliance Guide," that the Celacade's review would more than likely be moved to CBER. The agency recently confirmed the review change, Waddick said.

Vasogen also is developing a new class of drugs for the treatment of certain neuroinflammatory disorders. The firm's lead neuroinflammatory candidate is VP025, which successfully completed a double-blind, placebo-controlled Phase I trial in healthy volunteers.

The company is investigating VP025 as a potential treatment for Parkinson's disease, amyotrophic lateral sclerosis and diabetic retinopathy.